{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T20:47:49Z","timestamp":1791751669168,"version":"4.3.4"},"reference-count":105,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lykos Therapeutics","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) is currently being evaluated for treatment of patients with moderate or higher severity post-traumatic stress disorder (PTSD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To provide a comprehensive summary of investigational MDMA-AT and current treatments for PTSD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A search was conducted in PubMed and Embase (December 20, 2023). Populations included adults with chronic, treatment-resistant, moderate or higher severity PTSD. Interventions were MDMA-AT and comparators based on PTSD treatment guidelines. The primary outcome of interest was the Clinician-Administered PTSD Scale (CAPS) score. Other outcomes observed were Beck Depression Inventory (BDI), and loss of diagnosis (LOD). Studies observing chronic, moderate or higher severity treatment-resistant PTSD in adults were included. Only randomized controlled trials published in English were considered. The NICE quality appraisal checklist was used to assess risk of bias in included studies. We provided qualitative synthesis of evidence presented in extraction tables.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 77 studies were included. Phase II\/III trials consistently reported significantly greater CAPS improvement with MDMA-AT vs. placebo with therapy (PT) after two or three interventional sessions. Durability was observed in a long-term follow-up trial (mean duration, 45.4 months) with a 0.9-point CAPS decrease from post-treatment.<\/jats:p>\n                    <jats:p>FDA-approved and off-label medications used for PTSD treatment did not yield a consistently greater CAPS decrease vs. control arms across trials. Significant CAPS improvement was consistently observed in venlafaxine ER, olanzapine, propranolol (with traumatic memory reactivation), nefazodone, and nabilone placebo-controlled trials. Most psychotherapy trials lacked between-group statistical assessments. Significant CAPS decrease compared to the waitlist was reported for cognitive therapy (CT), cognitive behavioral therapy (CBT), cognitive processing therapy (CPT), prolonged exposure (PE), and group cognitive exposure therapy. CAPS improvement was persistent for CPT and PE in long-term follow up (mean duration 6.2 years).<\/jats:p>\n                    <jats:p>MDMA-AT demonstrated significant improvement in BDI-II score compared to PT (19.7-point vs. 10.8-point decrease, respectively; p\u2009=\u20090.003). The percentage of participants with LOD after two or three active-dose MDMA-AT sessions ranged from 41.7\u201383.3%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This systematic review suggests current treatments for PTSD are associated with heterogeneous evidence and the majority do not demonstrate sustained effects. Results from MDMA-AT showed consistent improvements in CAPS, BDI and LOD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0327778","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T17:38:55Z","timestamp":1752687535000},"page":"e0327778","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["MDMA-assisted therapy and current treatment options for chronic, treatment-resistant, moderate or higher severity post-traumatic stress disorder: Systematic literature review"],"prefix":"10.1371","volume":"20","author":[{"given":"Filip","family":"Stanicic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1368-4491","authenticated-orcid":true,"given":"Vladimir","family":"Zah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrije","family":"Grbic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djurdja","family":"Vukicevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"de Angelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"pone.0327778.ref001","volume-title":"Posttraumatic Stress Disorder","author":"SK Mann","year":"2022"},{"key":"pone.0327778.ref002","author":"JW Barnhill"},{"issue":"1","key":"pone.0327778.ref003","doi-asserted-by":"crossref","first-page":"7","DOI":"10.31887\/DCNS.2000.2.1\/bvdkolk","article-title":"Posttraumatic stress disorder and the nature of trauma","volume":"2","author":"B van der Kolk","year":"2000","journal-title":"Dialogues Clin Neurosci"},{"issue":"6","key":"pone.0327778.ref004","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24065238","article-title":"To predict, prevent, and manage post-traumatic stress disorder (PTSD): A review of pathophysiology, treatment, and biomarkers","volume":"24","author":"GI Al Jowf","year":"2023","journal-title":"Int J Mol Sci"},{"key":"pone.0327778.ref005","author":"US Department of Veterans Affairs"},{"key":"pone.0327778.ref006","author":"National Institute of Mental Health"},{"issue":"1","key":"pone.0327778.ref007","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3109\/00048670903393597","article-title":"Prevalence estimates of combat-related post-traumatic stress disorder: critical review","volume":"44","author":"LK Richardson","year":"2010","journal-title":"Aust N Z J Psychiatry"},{"issue":"3","key":"pone.0327778.ref008","doi-asserted-by":"crossref","DOI":"10.4088\/JCP.21m14116","article-title":"The Economic Burden of Posttraumatic Stress Disorder in the United States From a Societal Perspective","volume":"83","author":"LL Davis","year":"2022","journal-title":"J Clin Psychiatry"},{"issue":"5","key":"pone.0327778.ref009","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1037\/amp0000473","article-title":"Summary of the clinical practice guideline for the treatment of posttraumatic stress disorder (PTSD) in adults","volume":"74","author":"Guideline Development Panel for the Treatment of PTSD in Adults, American Psychological Association","year":"2019","journal-title":"Am Psychol"},{"issue":"5","key":"pone.0327778.ref010","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1001\/jama.2015.8370","article-title":"Psychotherapy for Military-Related PTSD: A Review of Randomized Clinical Trials","volume":"314","author":"MM Steenkamp","year":"2015","journal-title":"JAMA"},{"issue":"12","key":"pone.0327778.ref011","article-title":"Psychological therapies for chronic post-traumatic stress disorder (PTSD) in adults","volume":"2013","author":"JI Bisson","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"issue":"1","key":"pone.0327778.ref012","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1037\/tra0000062","article-title":"Time course of treatment dropout in cognitive-behavioral therapies for posttraumatic stress disorder","volume":"8","author":"CA Gutner","year":"2016","journal-title":"Psychol Trauma"},{"issue":"9","key":"pone.0327778.ref013","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/da.22511","article-title":"Psychotherapy versus pharmacotherapy for posttraumatic stress disorder: systemic review and meta-analyses to determine first-line treatments","volume":"33","author":"DJ Lee","year":"2016","journal-title":"Depress Anxiety"},{"key":"pone.0327778.ref014","volume-title":"A manual for MDMA-assisted psychotherapy in the treatment of posttraumatic stress disorder","author":"MC. Mithoefer","year":"2017"},{"issue":"6","key":"pone.0327778.ref015","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/s41591-021-01336-3","article-title":"MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study","volume":"27","author":"JM Mitchell","year":"2021","journal-title":"Nat Med"},{"issue":"10","key":"pone.0327778.ref016","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1038\/s41591-023-02565-4","article-title":"MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial","volume":"29","author":"JM Mitchell","year":"2023","journal-title":"Nature Medicine"},{"issue":"3","key":"pone.0327778.ref017","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1037\/pas0000486","article-title":"The clinician-administered PTSD scale for DSM-5 (CAPS-5): Development and initial psychometric evaluation in military veterans","volume":"30","author":"FW Weathers","year":"2018","journal-title":"Psychological Assessment"},{"key":"pone.0327778.ref018","unstructured":"American Psychological Association. Clinical practice guideline for the treatment of posttraumatic stress disorder (PTSD) in adults. 2017."},{"key":"pone.0327778.ref019","unstructured":"(VA\/DoD) Do VADoD. Clinical practice guideline for the management of posttraumatic stress disorder and acute stress disorder. 2017."},{"key":"pone.0327778.ref020","unstructured":"International Society for Traumatic Stress Studies ISTSS. Posttraumatic stress disorder prevention and treatment guidelines \u2013 methodology and recommendations. 2018."},{"key":"pone.0327778.ref021","author":"US Department of Veteran Affairs","year":"2023"},{"key":"pone.0327778.ref022","author":"Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)","year":"2023"},{"issue":"4","key":"pone.0327778.ref023","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1177\/0269881110378371","article-title":"The safety and efficacy of { \/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study","volume":"25","author":"MC Mithoefer","year":"2011","journal-title":"J Psychopharmacol"},{"issue":"6","key":"pone.0327778.ref024","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S2215-0366(18)30135-4","article-title":"3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial","volume":"5","author":"MC Mithoefer","year":"2018","journal-title":"Lancet Psychiatry"},{"issue":"12","key":"pone.0327778.ref025","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1177\/0269881118806297","article-title":"3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial","volume":"32","author":"M Ot\u2019alora G","year":"2018","journal-title":"J Psychopharmacol"},{"issue":"1","key":"pone.0327778.ref026","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1177\/0269881112464827","article-title":"A randomized, controlled pilot study of MDMA (\u00b1 3,4-methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic post-traumatic stress disorder (PTSD)","volume":"27","author":"P Oehen","year":"2013","journal-title":"J Psychopharmacol"},{"issue":"1","key":"pone.0327778.ref027","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1177\/0269881112456611","article-title":"Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study","volume":"27","author":"MC Mithoefer","year":"2013","journal-title":"J Psychopharmacol"},{"key":"pone.0327778.ref028","doi-asserted-by":"crossref","DOI":"10.1101\/2023.01.03.23284143","volume-title":"Self-experience in MDMA assisted therapy of PTSD","author":"BA van der Kolk","year":"2023"},{"key":"pone.0327778.ref029","first-page":"395","article-title":"The effectiveness of cognitive behavioral therapy with respect to psychological symptoms and recovering autobiographical memory in patients suffering from post-traumatic stress disorder","volume":"11","author":"F Akbarian","year":"2015","journal-title":"Neuropsychiatr Dis Treat"},{"issue":"9","key":"pone.0327778.ref030","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1017\/S0033291718002234","article-title":"Efficacy of exposure-based cognitive behaviour therapy for post-traumatic stress disorder in emergency service personnel: a randomised clinical trial","volume":"49","author":"RA Bryant","year":"2019","journal-title":"Psychol Med"},{"issue":"3","key":"pone.0327778.ref031","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1037\/0022-006X.73.3.515","article-title":"Randomized trial of cognitive-behavioral therapy for chronic posttraumatic stress disorder in adult female survivors of childhood sexual abuse","volume":"73","author":"A McDonagh","year":"2005","journal-title":"J Consult Clin Psychol"},{"issue":"7","key":"pone.0327778.ref032","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1001\/jama.2012.9307","article-title":"Effect of cognitive-behavioral couple therapy for PTSD: a randomized controlled trial","volume":"308","author":"CM Monson","year":"2012","journal-title":"JAMA"},{"key":"pone.0327778.ref033","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1017\/S135246589927302X","article-title":"Cognitive Behavioural Treatment of Post Traumatic Stress Disorder after Motor Vehicle Accident","volume":"27","author":"G Fecteau","year":"1999","journal-title":"Behavioural and Cognitive Psychotherapy"},{"issue":"1","key":"pone.0327778.ref034","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.beth.2008.01.003","article-title":"Group cognitive behavior therapy for chronic posttraumatic stress disorder: an initial randomized pilot study","volume":"40","author":"JG Beck","year":"2009","journal-title":"Behav Ther"},{"issue":"3","key":"pone.0327778.ref035","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/j.2051-5545.2011.tb00058.x","article-title":"A randomized controlled effectiveness trial of cognitive behavior therapy for post-traumatic stress disorder in terrorist-affected people in Thailand","volume":"10","author":"RA Bryant","year":"2011","journal-title":"World Psychiatry"},{"issue":"5","key":"pone.0327778.ref036","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/cpp.2194","article-title":"Randomized clinical trial pilot study of prolonged exposure versus present centred affect regulation therapy for PTSD and anger problems with male military combat veterans","volume":"25","author":"JD Ford","year":"2018","journal-title":"Clin Psychol Psychother"},{"issue":"4","key":"pone.0327778.ref037","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1017\/S1092852920001455","article-title":"A randomized clinical trial to assess the efficacy of trial-based cognitive therapy compared to prolonged exposure for post-traumatic stress disorder: preliminary findings","volume":"26","author":"\u00c9P Duran","year":"2021","journal-title":"CNS Spectr"},{"issue":"3","key":"pone.0327778.ref038","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1037\/tra0000111","article-title":"Group-delivered cognitive\/exposure therapy for PTSD in women veterans: A randomized controlled trial","volume":"8","author":"DT Castillo","year":"2016","journal-title":"Psychol Trauma"},{"issue":"9","key":"pone.0327778.ref039","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.4088\/JCP.09m05682blu","article-title":"Prolonged exposure therapy for combat- and terror-related posttraumatic stress disorder: a randomized control comparison with treatment as usual","volume":"72","author":"N Nacasch","year":"2011","journal-title":"J Clin Psychiatry"},{"issue":"1","key":"pone.0327778.ref040","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2021.36921","article-title":"Comparison of Prolonged Exposure vs Cognitive Processing Therapy for Treatment of Posttraumatic Stress Disorder Among US Veterans: A Randomized Clinical Trial","volume":"5","author":"PP Schnurr","year":"2022","journal-title":"JAMA Netw Open"},{"issue":"12","key":"pone.0327778.ref041","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1037\/ccp0000120","article-title":"Does timing matter? Examining the impact of session timing on outcome","volume":"84","author":"CA Gutner","year":"2016","journal-title":"J Consult Clin Psychol"},{"issue":"4","key":"pone.0327778.ref042","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1037\/0022-006X.70.4.867","article-title":"A comparison of cognitive-processing therapy with prolonged exposure and a waiting condition for the treatment of chronic posttraumatic stress disorder in female rape victims","volume":"70","author":"PA Resick","year":"2002","journal-title":"J Consult Clin Psychol"},{"issue":"2","key":"pone.0327778.ref043","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1037\/a0026602","article-title":"Long-term outcomes of cognitive-behavioral treatments for posttraumatic stress disorder among female rape survivors","volume":"80","author":"PA Resick","year":"2012","journal-title":"J Consult Clin Psychol"},{"issue":"3","key":"pone.0327778.ref044","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.janxdis.2012.01.006","article-title":"A multisite randomized controlled effectiveness trial of cognitive processing therapy for military-related posttraumatic stress disorder","volume":"26","author":"D Forbes","year":"2012","journal-title":"J Anxiety Disord"},{"issue":"2","key":"pone.0327778.ref045","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.janxdis.2013.12.002","article-title":"Comorbidity in the prediction of Cognitive Processing Therapy treatment outcomes for combat-related posttraumatic stress disorder","volume":"28","author":"D Lloyd","year":"2014","journal-title":"J Anxiety Disord"},{"issue":"5","key":"pone.0327778.ref046","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1037\/0022-006X.74.5.898","article-title":"Cognitive processing therapy for veterans with military-related posttraumatic stress disorder","volume":"74","author":"CM Monson","year":"2006","journal-title":"J Consult Clin Psychol"},{"key":"pone.0327778.ref047","doi-asserted-by":"crossref","first-page":"27414","DOI":"10.3402\/ejpt.v6.27414","article-title":"EMDR for Syrian refugees with posttraumatic stress disorder symptoms: results of a pilot randomized controlled trial","volume":"6","author":"C Acarturk","year":"2015","journal-title":"Eur J Psychotraumatol"},{"issue":"2","key":"pone.0327778.ref048","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1037\/0022-006X.71.2.330","article-title":"Comparative efficacy, speed, and adverse effects of three PTSD treatments: exposure therapy, EMDR, and relaxation training","volume":"71","author":"S Taylor","year":"2003","journal-title":"J Consult Clin Psychol"},{"issue":"1","key":"pone.0327778.ref049","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4088\/JCP.v68n0105","article-title":"A randomized clinical trial of eye movement desensitization and reprocessing (EMDR), fluoxetine, and pill placebo in the treatment of posttraumatic stress disorder: treatment effects and long-term maintenance","volume":"68","author":"BA van der Kolk","year":"2007","journal-title":"J Clin Psychiatry"},{"issue":"7604","key":"pone.0327778.ref050","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1136\/bmj.39021.846852.BE","article-title":"Post-traumatic stress disorder in the context of terrorism and other civil conflict in Northern Ireland: randomised controlled trial","volume":"334","author":"M Duffy","year":"2007","journal-title":"BMJ"},{"issue":"4","key":"pone.0327778.ref051","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.brat.2004.03.006","article-title":"Cognitive therapy for post-traumatic stress disorder: development and evaluation","volume":"43","author":"A Ehlers","year":"2005","journal-title":"Behav Res Ther"},{"issue":"12","key":"pone.0327778.ref052","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1176\/appi.ajp.158.12.1982","article-title":"Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study","volume":"158","author":"RD Marshall","year":"2001","journal-title":"Am J Psychiatry"},{"issue":"2","key":"pone.0327778.ref053","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/da.20176","article-title":"A controlled trial of paroxetine for chronic PTSD, dissociation, and interpersonal problems in mostly minority adults","volume":"24","author":"RD Marshall","year":"2007","journal-title":"Depress Anxiety"},{"issue":"1","key":"pone.0327778.ref054","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1176\/appi.ajp.2011.11020321","article-title":"Combined prolonged exposure therapy and paroxetine for PTSD related to the World Trade Center attack: a randomized controlled trial","volume":"169","author":"FR Schneier","year":"2012","journal-title":"Am J Psychiatry"},{"issue":"2","key":"pone.0327778.ref055","first-page":"84","article-title":"A comparison of mirtazapine and paroxetine for the treatment of patients with posttraumatic stress disorder: A randomized open-label trial","volume":"8","author":"HJ Seo","year":"2010","journal-title":"Clinical Psychopharmacology and Neuroscience"},{"issue":"2","key":"pone.0327778.ref056","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1097\/00004714-200204000-00013","article-title":"Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder","volume":"22","author":"J Zohar","year":"2002","journal-title":"J Clin Psychopharmacol"},{"issue":"5","key":"pone.0327778.ref057","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1001\/archpsyc.58.5.485","article-title":"Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder","volume":"58","author":"JR Davidson","year":"2001","journal-title":"Arch Gen Psychiatry"},{"issue":"2","key":"pone.0327778.ref058","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1001\/jamapsychiatry.2018.3412","article-title":"Efficacy of Prolonged Exposure Therapy, Sertraline Hydrochloride, and Their Combination Among Combat Veterans With Posttraumatic Stress Disorder: A Randomized Clinical Trial","volume":"76","author":"SAM Rauch","year":"2019","journal-title":"JAMA Psychiatry"},{"issue":"3","key":"pone.0327778.ref059","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/01.jcp.0000222514.71390.c1","article-title":"Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study","volume":"26","author":"J Davidson","year":"2006","journal-title":"J Clin Psychopharmacol"},{"issue":"6","key":"pone.0327778.ref060","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1056\/NEJMoa1507598","article-title":"Trial of prazosin for post-traumatic stress disorder in military veterans","volume":"378","author":"MA Raskind","year":"2018","journal-title":"N Engl J Med"},{"issue":"2","key":"pone.0327778.ref061","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1176\/appi.ajp.160.2.371","article-title":"Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study","volume":"160","author":"MA Raskind","year":"2003","journal-title":"Am J Psychiatry"},{"issue":"8","key":"pone.0327778.ref062","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.biopsych.2006.06.032","article-title":"A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder","volume":"61","author":"MA Raskind","year":"2007","journal-title":"Biol Psychiatry"},{"issue":"9","key":"pone.0327778.ref063","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1176\/appi.ajp.2013.12081133","article-title":"A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan","volume":"170","author":"MA Raskind","year":"2013","journal-title":"Am J Psychiatry"},{"issue":"6","key":"pone.0327778.ref064","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1176\/appi.ajp.2014.13121625","article-title":"A randomized, double-blind evaluation of D-cycloserine or alprazolam combined with virtual reality exposure therapy for posttraumatic stress disorder in Iraq and Afghanistan War veterans","volume":"171","author":"BO Rothbaum","year":"2014","journal-title":"Am J Psychiatry"},{"issue":"5","key":"pone.0327778.ref065","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1038\/npp.2013.317","article-title":"D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial","volume":"39","author":"J Difede","year":"2014","journal-title":"Neuropsychopharmacology"},{"issue":"11","key":"pone.0327778.ref066","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.biopsych.2012.02.033","article-title":"A randomized placebo-controlled trial of D-cycloserine to enhance exposure therapy for posttraumatic stress disorder","volume":"71","author":"RA de Kleine","year":"2012","journal-title":"Biol Psychiatry"},{"issue":"5","key":"pone.0327778.ref067","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.biopsych.2004.11.039","article-title":"Adjunctive risperidone in the treatment of chronic combat-related posttraumatic stress disorder","volume":"57","author":"G Bartzokis","year":"2005","journal-title":"Biol Psychiatry"},{"issue":"5","key":"pone.0327778.ref068","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1001\/jama.2011.1080","article-title":"Adjunctive risperidone treatment for antidepressant-resistant symptoms of chronic military service-related PTSD: a randomized trial","volume":"306","author":"JH Krystal","year":"2011","journal-title":"JAMA"},{"issue":"5","key":"pone.0327778.ref069","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/00004850-200609000-00005","article-title":"Risperidone monotherapy for post-traumatic stress disorder related to sexual assault and domestic abuse in women","volume":"21","author":"PR Padala","year":"2006","journal-title":"Int Clin Psychopharmacol"},{"issue":"5","key":"pone.0327778.ref070","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.euroneuro.2005.10.007","article-title":"Fluoxetine in the acute treatment and relapse prevention of combat-related post-traumatic stress disorder: Analysis of the veteran group of a placebo-controlled, randomized clinical trial","volume":"16","author":"F Martenyi","year":"2006","journal-title":"Eur Neuropsychopharmacol"},{"issue":"2","key":"pone.0327778.ref071","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1097\/JCP.0b013e31803308ce","article-title":"Failed efficacy of fluoxetine in the treatment of posttraumatic stress disorder: results of a fixed-dose, placebo-controlled study","volume":"27","author":"F Martenyi","year":"2007","journal-title":"J Clin Psychopharmacol"},{"issue":"5","key":"pone.0327778.ref072","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1755-5949.2010.00188.x","article-title":"A double-blind randomized controlled trial to study the efficacy of topiramate in a civilian sample of PTSD","volume":"17","author":"MSL Yeh","year":"2011","journal-title":"CNS Neurosci Ther"},{"issue":"5","key":"pone.0327778.ref073","article-title":"Topiramate Monotherapy for Civilian Posttraumatic Stress Disorder: A Controlled Pilot Study","volume":"25","author":"V Monga","year":"2023","journal-title":"Prim Care Companion CNS Disord"},{"issue":"10","key":"pone.0327778.ref074","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1001\/archpsyc.63.10.1158","article-title":"Treatment of posttraumatic stress disorder with venlafaxine extended release: a 6-month randomized controlled trial","volume":"63","author":"J Davidson","year":"2006","journal-title":"Arch Gen Psychiatry"},{"issue":"9","key":"pone.0327778.ref075","article-title":"Randomized placebo-controlled trial of propranolol plus traumatic memory reactivation for PTSD","volume":"75","author":"A Brunet","year":"2014","journal-title":"Biological Psychiatry"},{"issue":"5","key":"pone.0327778.ref076","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1176\/appi.ajp.2017.17050481","article-title":"Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A Randomized Controlled Trial","volume":"175","author":"A Brunet","year":"2018","journal-title":"Am J Psychiatry"},{"issue":"7","key":"pone.0327778.ref077","doi-asserted-by":"crossref","first-page":"892","DOI":"10.4088\/JCP.09m05607gry","article-title":"Eszopiclone for the treatment of posttraumatic stress disorder and associated insomnia: a randomized, double-blind, placebo-controlled trial","volume":"72","author":"MH Pollack","year":"2011","journal-title":"J Clin Psychiatry"},{"issue":"3","key":"pone.0327778.ref078","doi-asserted-by":"crossref","first-page":"21","DOI":"10.5498\/wjp.v10.i3.21","article-title":"Double-blind randomized controlled study of the efficacy, safety and tolerability of eszopiclone vs placebo for the treatment of patients with post-traumatic stress disorder and insomnia","volume":"10","author":"SM Dowd","year":"2020","journal-title":"World J Psychiatry"},{"issue":"8","key":"pone.0327778.ref079","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1038\/s41386-022-01266-9","article-title":"Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial","volume":"47","author":"CG Abdallah","year":"2022","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"pone.0327778.ref080","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/JCP.0b013e318160f83b","article-title":"Divalproex in the treatment of posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial in a veteran population","volume":"28","author":"LL Davis","year":"2008","journal-title":"J Clin Psychopharmacol"},{"key":"pone.0327778.ref081","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.psyneuen.2014.11.002","article-title":"The efficacy of nabilone, a synthetic cannabinoid, in the treatment of PTSD-associated nightmares: A preliminary randomized, double-blind, placebo-controlled cross-over design study","volume":"51","author":"R Jetly","year":"2015","journal-title":"Psychoneuroendocrinology"},{"issue":"15","key":"pone.0327778.ref082","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1007\/s00213-017-4649-y","article-title":"A randomized controlled trial of ganaxolone in posttraumatic stress disorder","volume":"234","author":"AM Rasmusson","year":"2017","journal-title":"Psychopharmacology (Berl)"},{"issue":"4","key":"pone.0327778.ref083","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/hup.2238","article-title":"Olanzapine monotherapy in posttraumatic stress disorder: efficacy in a randomized, double-blind, placebo-controlled study","volume":"27","author":"P Carey","year":"2012","journal-title":"Hum Psychopharmacol"},{"key":"pone.0327778.ref084","doi-asserted-by":"crossref","first-page":"113974","DOI":"10.1016\/j.psychres.2021.113974","article-title":"Randomized clinical trial of bedtime sublingual cyclobenzaprine (TNX-102 SL) in military-related PTSD and the role of sleep quality in treatment response","volume":"301","author":"GM Sullivan","year":"2021","journal-title":"Psychiatry Res"},{"issue":"3","key":"pone.0327778.ref085","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1097\/01.jcp.0000125685.82219.1a","article-title":"A placebo-controlled study of nefazodone for the treatment of chronic posttraumatic stress disorder: a preliminary study","volume":"24","author":"LL Davis","year":"2004","journal-title":"J Clin Psychopharmacol"},{"issue":"5","key":"pone.0327778.ref086","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2023.10223","article-title":"Efficacy and Safety of Mifepristone in the Treatment of Male US Veterans With Posttraumatic Stress Disorder: A Phase 2a Randomized Clinical Trial","volume":"6","author":"JA Golier","year":"2023","journal-title":"JAMA Netw Open"},{"issue":"1","key":"pone.0327778.ref087","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1097\/JCP.0b013e31802e5115","article-title":"The efficacy and tolerability of tiagabine in adult patients with post-traumatic stress disorder","volume":"27","author":"JRT Davidson","year":"2007","journal-title":"J Clin Psychopharmacol"},{"issue":"4","key":"pone.0327778.ref088","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1192\/bjp.bp.115.167775","article-title":"Eye movement desensitisation and reprocessing therapy v. stabilisation as usual for refugees: randomised controlled trial","volume":"209","author":"FJJ Ter Heide","year":"2016","journal-title":"Br J Psychiatry"},{"issue":"2","key":"pone.0327778.ref089","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/13651501.2017.1291838","article-title":"Effect and safety of sertraline for treat posttraumatic stress disorder: a multicenter randomised controlled study","volume":"21","author":"W Li","year":"2017","journal-title":"Int J Psychiatry Clin Pract"},{"issue":"10","key":"pone.0327778.ref090","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1017\/S0033291711000201","article-title":"A randomized, double-blind, placebo-controlled trial on the efficacy and tolerability of sertraline in Iranian veterans with post-traumatic stress disorder","volume":"41","author":"Y Panahi","year":"2011","journal-title":"Psychol Med"},{"issue":"2","key":"pone.0327778.ref091","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S0006-3223(02)01411-7","article-title":"Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial","volume":"53","author":"JR Davidson","year":"2003","journal-title":"Biol Psychiatry"},{"issue":"5","key":"pone.0327778.ref092","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1037\/0022-006X.73.5.953","article-title":"Randomized trial of prolonged exposure for posttraumatic stress disorder with and without cognitive restructuring: outcome at academic and community clinics","volume":"73","author":"EB Foa","year":"2005","journal-title":"J Consult Clin Psychol"},{"issue":"1","key":"pone.0327778.ref093","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1186\/s12888-021-03441-6","article-title":"Tackling the global problem of traumatic stress in low-income countries: a pilot clinical trial comparing reconsolidation therapy to paroxetine in Nepal","volume":"21","author":"A Brunet","year":"2021","journal-title":"BMC Psychiatry"},{"issue":"5","key":"pone.0327778.ref094","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/jts.20170","article-title":"Augmentation of sertraline with prolonged exposure in the treatment of posttraumatic stress disorder","volume":"19","author":"BO Rothbaum","year":"2006","journal-title":"J Trauma Stress"},{"issue":"6","key":"pone.0327778.ref095","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1097\/jcp.0b013e31815a43ee","article-title":"A randomized, double-blind, placebo-controlled trial of augmentation topiramate for chronic combat-related posttraumatic stress disorder","volume":"27","author":"SE Lindley","year":"2007","journal-title":"J Clin Psychopharmacol"},{"issue":"2","key":"pone.0327778.ref096","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0278-5846(01)00282-2","article-title":"Tolerability of fluoxetine in posttraumatic stress disorder","volume":"26","author":"SD Barnett","year":"2002","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"issue":"2","key":"pone.0327778.ref097","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/jts.22479","article-title":"Posttraumatic Growth After MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder","volume":"33","author":"I Gorman","year":"2020","journal-title":"J Trauma Stress"},{"issue":"4","key":"pone.0327778.ref098","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/jts.22696","article-title":"Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder","volume":"34","author":"L Ponte","year":"2021","journal-title":"J Trauma Stress"},{"issue":"2","key":"pone.0327778.ref099","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1192\/bjp.bp.114.148551","article-title":"Pharmacotherapy for post-traumatic stress disorder: systematic review and meta-analysis","volume":"206","author":"M Hoskins","year":"2015","journal-title":"Br J Psychiatry"},{"issue":"1","key":"pone.0327778.ref100","doi-asserted-by":"crossref","first-page":"1729633","DOI":"10.1080\/20008198.2020.1729633","article-title":"Psychological therapies for post-traumatic stress disorder in adults: systematic review and meta-analysis","volume":"11","author":"C Lewis","year":"2020","journal-title":"Eur J Psychotraumatol"},{"key":"pone.0327778.ref101","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.cpr.2015.10.003","article-title":"Psychological treatments for adults with posttraumatic stress disorder: A systematic review and meta-analysis","volume":"43","author":"K Cusack","year":"2016","journal-title":"Clin Psychol Rev"},{"issue":"1","key":"pone.0327778.ref102","doi-asserted-by":"crossref","first-page":"1709709","DOI":"10.1080\/20008198.2019.1709709","article-title":"Dropout from psychological therapies for post-traumatic stress disorder (PTSD) in adults: systematic review and meta-analysis","volume":"11","author":"C Lewis","year":"2020","journal-title":"Eur J Psychotraumatol"},{"issue":"2","key":"pone.0327778.ref103","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1080\/13607863.2014.920299","article-title":"Post-traumatic stress disorder in older adults: a systematic review of the psychotherapy treatment literature","volume":"19","author":"S Dinnen","year":"2015","journal-title":"Aging Ment Health"},{"key":"pone.0327778.ref104","author":"Multidisciplinary Association for Psychedelic Studies (MAPS)"},{"key":"pone.0327778.ref105","author":"American Journal of Managed Care (AJMC)","year":"2023"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0327778","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T17:39:10Z","timestamp":1752687550000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0327778"}},"subtitle":[],"editor":[{"given":"Giuseppe","family":"Carr\u00e0","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,7,16]]},"references-count":105,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0327778","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,16]]}}}